A summary of progress and an outline for future study in support of our "two-route" approach to the total synthesis of the potent antileukemia agents Bruceantinol and Bruceantin are detailed. The approach is flexible and is designed to provide numerous substrates for pharmacological testing and for the exploration of structure-activity relationships. The chemistry stresses a stereocontrolled synthesis with particular emphasis on intramolecular reactions such as a new annulation approach to enones ("Robinson-Transposition" reaction), as well as a route which utilizes an axial thiomethyl control element to direct the establishment of five contiguous asymmetric centers.